1. Technical Field of the Invention
The present invention relates to a novel class of biaromatic compounds which are activators of receptors of “Peroxisome Proliferator-Activated Receptor” type of subtype γ (PPARγ). This invention also relates to their process of preparation and to their formulation into pharmaceutical compositions suited for human or veterinary medicine, or alternatively for cosmetic compositions.
2. Description of Background and/or Related and/or Prior Art:
The activity of receptors of PPAR type has been the subject of many studies. Mention may be made, by way of indication, of the publication entitled “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol., 1998, 111, 1116-1121, in which a large number of bibliographic references relating to receptors of PPAR type are listed. Mention may also be made, by way of indication, of the report entitled “The PPARs: From Orphan Receptors to Drug Discovery”, Timothy M. Willson et al., J. Med. Chem., 2000, 43, 527-550.
PPAR receptors activate transcription by binding to elements of DNA sequences, known as peroxisome proliferator response elements (PPRE), in the form of a heterodimer with retinoid X receptors (known as RXRs).
Three subtypes of human PPARs have been identified and described: PPARα, PPARγ and PPARδ (or NUC1).
PPARα is mainly expressed in the liver, while PPARδ is ubiquitous.
PPARγ is the most widely studied of the three subtypes. All prior art references suggest a critical role for PPARγ in the regulation of the differentiation of adipocytes, where it is greatly expressed. It also plays a key role in systemic lipid homeostasis.
Furthermore, the assignee hereof has already disclosed, in FR 98/02894, the use of PPARγ-activating compounds in the preparation of a pharmaceutical composition, the composition being intended for the treatment of skin disorders related to an anomaly in the differentiation of the epidermal cells.
The assignee hereof has also disclosed a class of biaromatic compounds which are activators of PPARγ receptors in FR-2,812,876.